NYMC Faculty Publications
Metabolic Deregulation in Pulmonary Hypertension
Author Type(s)
Faculty
DOI
10.3390/cimb45060309
Journal Title
Current Issues in Molecular Biology
First Page
4850
Last Page
4874
Document Type
Article
Publication Date
6-3-2023
Department
Pediatrics
Abstract
The high morbidity and mortality rate of pulmonary arterial hypertension (PAH) is partially explained by metabolic deregulation. The present study complements our previous publication in "Genes" by identifying significant increases of the glucose transporter solute carrier family 2 (Slc2a1), beta nerve growth factor (Ngf), and nuclear factor erythroid-derived 2-like 2 (Nfe2l2) in three standard PAH rat models. PAH was induced by subjecting the animals to hypoxia (HO), or by injecting with monocrotaline in either normal (CM) or hypoxic (HM) atmospheric conditions. The Western blot and double immunofluorescent experiments were complemented with novel analyses of previously published transcriptomic datasets of the animal lungs from the perspective of the Genomic Fabric Paradigm. We found substantial remodeling of the citrate cycle, pyruvate metabolism, glycolysis/gluconeogenesis, and fructose and mannose pathways. According to the transcriptomic distance, glycolysis/gluconeogenesis was the most affected functional pathway in all three PAH models. PAH decoupled the coordinated expression of many metabolic genes, and replaced phosphomannomutase 2 (Pmm2) with phosphomannomutase 1 (Pmm1) in the center of the fructose and mannose metabolism. We also found significant regulation of key genes involved in PAH channelopathies. In conclusion, our data show that metabolic dysregulation is a major PAH pathogenic factor.
Recommended Citation
Mathew, R., Iacobas, S., Huang, J., & Iacobas, D. A. (2023). Metabolic Deregulation in Pulmonary Hypertension. Current Issues in Molecular Biology, 45 (6), 4850-4874. https://doi.org/10.3390/cimb45060309
